Wnt Signaling Regulates Multipolar-to-Bipolar Transition of Migrating Neurons in the Cerebral Cortex

• Published in: Cell reports (Cambridge) Vol. 10; no. 8; pp. 1349 - 1361
• Main Authors: Boitard, Michael, Bocchi, Riccardo, Egervari, Kristof, Petrenko, Volodymyr, Viale, Beatrice, Gremaud, Stéphane, Zgraggen, Eloisa, Salmon, Patrick, Kiss, Jozsef Z.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.03.2015; Elsevier
• Subjects: Animals; beta Catenin - metabolism; Cell Movement; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Ephrin-B1 - metabolism; Microscopy, Fluorescence; Neurons - cytology; Neurons - metabolism; Neurons - pathology; Pyramidal Cells - cytology; Pyramidal Cells - metabolism; Rats; Rats, Wistar; RNA Interference; RNA, Small Interfering - metabolism; T-Box Domain Proteins - metabolism; Time-Lapse Imaging; Wnt Proteins - antagonists & inhibitors; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway; Wnt-5a Protein
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.01.061

The precise timing of pyramidal cell migration from the ventricular germinal zone to the cortical plate is essential for establishing cortical layers, and migration errors can lead to neurodevelopmental disorders underlying psychiatric and neurological diseases. Here, we report that Wnt canonical as well as non-canonical signaling is active in pyramidal precursors during radial migration. We demonstrate using constitutive and conditional genetic strategies that transient downregulation of canonical Wnt/β-catenin signaling during the multipolar stage plays a critical role in polarizing and orienting cells for radial migration. In addition, we show that reduced canonical Wnt signaling is triggered cell autonomously by time-dependent expression of Wnt5A and activation of non-canonical signaling. We identify ephrin-B1 as a canonical Wnt-signaling-regulated target in control of the multipolar-to-bipolar switch. These findings highlight the critical role of Wnt signaling activity in neuronal positioning during cortical development. [Display omitted] •Canonical and non-canonical Wnt signaling is active in migrating pyramidal neurons•Downregulation of canonical Wnt signaling is permissive for neuronal polarization•Canonical Wnt signaling is reduced by an increase in Wnt5A/non-canonical signaling•This allows cellular ephrin-B1 expression, thereby enabling neuronal polarization Boitard et al. demonstrate that transient downregulation of canonical Wnt/β-catenin signaling during the multipolar stage plays a critical permissive role for polarizing and orienting cells for radial migration. This downregulation is initiated cell autonomously by time-dependent expression of Wnt5A and activation of non-canonical signaling enabling ephrin-B1 expression.